Pre-transition effects mediate forces of assembly between transmembrane proteins

Area of Science:

• Biophysics
• Membrane Biology
• Computational Biology

Background:

• Transmembrane proteins play vital roles in cell function.
• Understanding protein assembly and mobility in lipid bilayers is essential for deciphering biological processes.
• Existing models do not fully explain the forces governing protein interactions within membranes.

Purpose of the Study:

• To elucidate a novel mechanism for transmembrane protein assembly and mobility in lipid bilayers.
• To characterize the 'orderphobic effect' and its dependence on membrane phase transitions.
• To quantify the forces driving protein interactions and compare them to membrane elasticity.

Main Methods:

• Large-scale molecular dynamics simulations were employed to model protein-lipid interactions.
• Analysis focused on the stabilization of order-disorder interfaces in lipid bilayers.
• The energetic contributions to protein assembly were calculated.

Main Results:

• A protein with hydrophobic thickness matching the disordered phase stabilizes a microscopic order-disorder interface in an ordered bilayer.
• This interface possesses finite stiffness, leading to attractive forces between proteins.
• The 'orderphobic effect' drives protein assembly by reducing net interfacial energy.

Conclusions:

• The 'orderphobic effect' provides a powerful, generic mechanism for transmembrane protein assembly and mobility.
• This force is mediated by proximity to the membrane's order-disorder phase transition and protein characteristics.
• The identified forces are significantly stronger and longer-ranged than those predicted by membrane elasticity alone.